Utility of Time-Resolved MR Angiography in Clinical Practice

Image Gallery

Dr. Lohan
is a Diagnostic Cardiovascular Imaging Fellow,
Dr. Saleh
is a Research Fellow,
Dr. Tomasian
is a Research Fellow,
Dr. Krishnam
is an Assistant Professor of Radiology, and
Dr. Finn
is a Professor of Radiology and Medicine, Chief of Diagnostic
Cardiovascular Imaging, and Director of Magnetic Resonance
Research, Department of Radiology, David Geffen School of
Medicine at University of California, Los Angeles, CA.

Steady improvements in the performance of contrast-enhanced MR
angiography (CE-MRA) have, in recent years, resulted in its more
widespread adoption as a routine clinical tool. As widely used,
CE-MRA uses 3-dimensional (3D) data acquisition with measurement
times on the order of 20 to 40 seconds. For many applications that
involve the assessment of vascular patency or stenosis, this
approach is entirely appropriate. In most cases, accurate timing of
the contrast bolus can be assured by the use of a test injection,
such that a high spatial resolution acquisition is planned to
coincide with the peak of the contrast bolus.
1,2

The accuracy of CE-MRA has been well established in several
vascular territories.
3,4
The more recent availability of 3T scanners has pushed the
boundaries of speed and spatial resolution, and this trend seems
set to continue with the increasing use of radiofrequency
acceleration techniques. Submillimeter voxel dimensions over large
fields of view (FOVs) can be acquired within a breath-hold period,
for artifact-free evaluation of the thorax, abdomen, and
supra-aortic arteries.
5-7

A complementary approach to imaging a contrast bolus involves
multiple measurements repeated rapidly to document the first pass
of the bolus through the various compartments of the circulation.
This has become known as time-resolved MRA (TR-MRA), and it can be
used to provide dynamic or functional information that is not
available from a conventional single-phase MRA. A number of
practical implementations of TR-MRA have been described, each with
its advantages, drawbacks, and system requirements. In this
article, we will describe our experience with one class of TR-MRA
and emphasize that other approaches are also possible.

Time-resolved MRA allows confident separation of arterial and
venous phases of vascular enhancement and provides intuitive
information regarding directional and temporal parenchymal
perfusion. Quantitative surrogates of organ perfusion in the form
of time-to-peak (TTP) signal intensity, maximal upslope of the
curve (MUS), maximal signal intensity (MSI), and mean transit time
(MTT) can be readily derived from dynamic angiographic data.
8
Considering the heightened awareness of potential side effects of
the use of contrast media in patients with renal failure, the
potential contrast dose reduction using TR-MRA is particularly
beneficial. Many of the current regimens use contrast doses as low
as 0.05 mmol/kg.
8
This article considers the underlying principles of TR-MRA,
exploring several current applications of this technique in
clinical practice.

Technical considerations

Dynamic, first-pass imaging of a contrast bolus has been
extensively studied; it was initially performed with a
2-dimensional (2D) projectional technique,
9
sometimes with repeated injection of small contrast doses.
10
More recently, 3D TR-MRA has been described for a number of
clinical applications.
8,11-13
Two broad approaches to 3D TR-MRA have been pursued; the first
approach generates speed by compromising on through-plane
resolution,
14
and the other generates speed by compromising on temporal
resolution of high spatial frequency components.
15
A third approach, still under development, is to use a 3D,
spherical k-space acquisition with extensive temporal sharing of
high spatial frequency components.
16
In this article, we will address variants of the first
category.

Irrespective of its specific implementation, TR-MRA involves
rapid sequential T1-weighted imaging of a vascular territory during
the dynamic passage of the contrast bolus. Very fast image
acquisition usually involves a 3D, spoiled gradient-echo sequence
with ultra short repetition time (<2 msec) and echo time (TE)
(<1 msec). The imaging parameters that influence in-plane
spatial resolution, through-plane resolution, frame rate, and FOV
can be adjusted, depending on the clinical application. Advances in
gradient and radiofrequency hardware, in combination with stronger
magnets, have laid the foundation for highly improved performance
of TR-MRA. Specific advances involve parallel imaging and temporal
echo sharing in various combinations.
17,18

Parallel imaging

Parallel imaging makes use of the spatially dependent
sensitivities of individual elements in a receiver coil array to
substitute for some of the spatial encoding previously performed
only by the gradients.
18,19
The spatial sensitivity of each distinct coil element provides
signal that is unique to its location within the FOV. In so doing,
this approach substitutes for some phase-encoding steps, with coil
sensitivity profiles providing the remaining data.

Several reconstruction algorithms have been devised and
proposed, and these may be broadly classified according to whether
they work in the image domain (sensitivity-encoding [SENSE],
partially parallel imaging with localized sensitivities [PILS], in
which the missing data are added after Fourier transformation), the
Fourier (k-space) domain (simultaneous acquisition of spatial
harmonics [SMASH], a self-calibrating technique for SMASH imaging
[AUTO-SMASH], generalized auto-calibrating partially parallel
acquisition [GRAPPA], whereby the missing k-space data are
calculated prior to Fourier transformation), or a combination of
both (sensitivity profiles from an array of coils for encoding and
reconstruction in parallel (SPACE RIP) and generalized SENSE). At
the present time, only SENSE (array spatial sensitivity-encoding
technique [ASSET]) and GRAPPA are available for clinical
application. Parallel imaging may be used to increase spatial
resolution and/or coverage, without prolonging image acquisition
time. Although 3D TR-MRA in subsecond time frames was originally
described without parallel imaging,
14
the use of parallel imaging facilitates increased coverage and/or
spatial resolution when imaging transient phenomena.
20
Parallel imaging can increase the performance of CE-MRA
several-fold, depending on the application.
21-24
Combining temporal echo sharing (time-resolved imaging of contrast
kinetics [TRICKS], time-resolved echo-shared angiographic technique
[TREAT], time-resolved angiography with interleaved stochastic
trajectories [TWIST]) with parallel acquisition can increase the
apparent temporal resolution further, typically by approximately
30%.
25,26

Clinical applications of contrast-enhanced
TR-MRA

Time-resolved MRA has been successfully applied to a variety of
anatomic regions, with very positive results. In our practice, we
generally use TR-MRA prior to performing high spatial resolution
MRA, in order to provide additional functional information. For
TR-MRA, we use only a very small dose of contrast (2 to 4 mL), so
that there is little incremental cost, time, or risk to the
patient.

Head and neck TR-MRA

Caroticovertebral and intracranial MRA is challenging and very
important. The feasibility of intracranial TR-MRA was initially
demonstrated by Wang et al,
27
using a 2D technique in 28 patients with a temporal resolution of
2.2 seconds. Klisch
10
used a similar technique in 4 patients with cerebral arteriovenous
malformations and dural arteriovenous fistulae, before and after
intravascular embolization, concluding that temporal evaluation
provided invaluable data with regard to the hemodynamics of such
shunting. Lenhart
28
evaluated the diagnostic accuracy of 3D carotid arterial TR- MRA at
1.5T, compared with the gold standard of selective catheter
angiography. These authors performed 4 consecutive measurements,
each with a duration of 10 seconds, isolated the arterial phase in
all 43 patients, and reported a sensitivity and specificity for the
detection of >70% stenoses of 98% and 86%, respectively. By
today's standards, a temporal resolution of 10 seconds is modest.
Further advances in gradient coils, multielement detector arrays,
parallel imaging, and sequence design facilitated the application
of TR-MRA to the assessment of extracranial-to-intracranial bypass
grafts
29
as well as to various craniocervical vascular disorders,
30
with temporal resolution approximating 1 second per frame (Figure
1). The improved temporal resolution also facilitated the
evaluation of regional flow dynamics, including
signal-intensity-over-time curves and TTP enhancement, parameters
of value in the differentiation of cervical glomus tumors from
hypovascularized malignant tumors, as reported by Michaely et al.
31
More recently, the availability of 3T systems has further advanced
the versatility of TR-MRA, facilitating increased spatial
resolution over large FOVs at ever-decreasing contrast doses.
20
The full potential of 3T head and neck TR-MRA is yet to be
realized.

Pulmonary TR-MRA

Finn et al
14
performed pulmonary arterial dynamic imaging with acquisition times
of 800 msec using gadolinium contrast doses as small as 6 mL. Fink
et al
32
later confirmed the improvements in image quality in their observer
preference study comparing echo-shared parallel TR-MRA of the lung
with non-echo-shared sequences, determining the former to achieve
higher spatial resolution, which was ultimately perceived as
improved image quality. More recently, TR-MRA has been applied to
acutely ill patients with suspected pulmonary embolism. Ersoy et al
33
confirmed that consistent arterial-phase imaging, which is capable
of allowing confident diagnosis from the main pulmonary artery
through the segmental branches, has potential value as a screening
examination in patients with contraindications to the use of
iodinated contrast material.

The technical feasibility of pulmonary TR-MRA has also been
shown at 3T, with comparable perfusion and flow indices at this
field strength as at 1.5T.
11
Nael et al
34
reported confident visualization up to the fourth-order pulmonary
arterial branches using TR-MRA, compared with fifth-order branches
using high-resolution CE-MRA, thus providing high vascular
morphologic detail and dynamic functional information, of
particular utility in patients with pulmonary arterial
hypertension.

As discussed above, TR-MRA allows clear separation of arterial
and venous phases of enhancement during a single contrast bolus
injection. Körperich et al
35
confirmed the utility of this technique in the evaluation of
pulmonary venous return after radiofrequency pulmonary vein
isolation for atrial fibrillation.

Abdominal TR-MRA

Abdominal visceral imaging has also benefited from the TR-MRA.
For renal perfusion imaging, TR-MRA has been reported to be 92.9%
sensitive, 83.4% specific, and 85.9% accurate in the detection of
significant renal artery stenosis.
36
Additionally, the evaluation of first-pass contrast kinetics may
provide valuable dynamic and functional information. While a number
of MR sequences have been evaluated in this regard-detailed
discussion of which is beyond the scope of this article- studies
that have investigated the utility of TREAT have found it equally
feasible to saturation recovery turbo fast low-angle shot
(SR-TurboFLASH) at 1.5T and 3T, yielding additional anatomic and
functional information about the renal vasculature.
37

In addition, TR-MRA has been successfully applied to the
assessment of other intra-abdominal viscera, including the hepatic
arterial and portal venous anatomy in living liver donors, in whom
confident separation of the arterial and venous phases of hepatic
enhancement proved to be of considerable benefit in the assessment
of feeding vessels and portal venous anatomy.
38
Similarly, it has a potential role in the detection and
classification of the transient phenomenon that is aortic endoleak.
In patients with an endovascular stent graft deployment, TR-MRA
outperformed CT angiography in the detection of endoleak and
provided results comparable to conventional angiography, without
arterial puncture or ionizing radiation exposure (Figure 2).
39

Peripheral TR-MRA

One of the technical challenges associated with peripheral MR
angiography is the synchronization of data acquisition with the
arrival of the contrast bolus within the vessels of interest such
that the center of k-space corresponds with peak vascular luminal
enhancement. This is of particular importance with regard to the
trifurcation vessels, in which premature image acquisition results
in suboptimal vascular enhancement, and late acquisition results in
venous contamination. This may be further compounded by the
presence of differential vascular filling between the 2 limbs or
within a single extremity, due to the presence of proximal
significant stenosis (Figure 3).

Several investigators have evaluated the utility of
time-resolved imaging of the calves as a means of obviating the
need for bolus-imaging coordination. Mell et al
40
compared dynamic TR-MRA of the infrapopliteal arterial segment to
conventional digital subtraction angiography in 27 patients with
peripheral steno-occlusive disease. With 7-second temporal
resolution, these authors found that TR-MRA had a sensitivity of
94% and a specificity of 92% for the detection of significant
stenoses in the popliteal artery, with a sensitivity of 100% and a
specificity of 84% for the tibial arteries. These findings closely
echoed those of Swan et al
41
in their study performed several years previously in a group of 69
patients with suspected arterial occlusive disease. The superiority
of TR-MRA to time-of-flight MRA for distal lower extremity imaging
was subsequently confirmed by Hahn,
42
who determined that this approach to yield results was
statistically indistinguishable from those of 3D bolus-chase
CE-MRA. Similarly encouraging results have been obtained with
application of this technique to the assessment of the upper
extremity vasculature, providing functional information in lesions
with rapid blood flow, such as hemangiomata.
43

While most often used as a means of reliable prevention of
venous contamination during the arterial phase of peripheral
imaging, the potential role of TR-MRA in the evaluation of the
lower extremity venous system has also been assessed. Successful
dynamic isolated venous-phase lower extremity imaging has been
reported by Du et al
44
using an automated segmentation algorithm based on a contrast
arrival time threshold, confirming the potential for both arterial
and venous-phase peripheral vascular imaging using a
single-injection technique.

TR-MRA in congenital heart disease

Even allowing for the multiplanar imaging capabilities of MRI,
detailed assessment of congenital heart disease-in particular the
integrity of postoperative shunts and conduits-remains a
considerable challenge for modern imaging techniques. While CT
angiography and MRA are often adequate for confirmation of chamber
patency, the detection of directional flow and of subtle
pulmonary-systemic shunts often remains beyond the capabilities of
"static" imaging techniques. The potential utility of TR-MRA has
been recognized with regard to assessing these parameters in the
presence of congenital heart disease (Figure 4), with encouraging
results in the evaluation of Fontan circulation or bidirectional
cavopulmonary connections where the details regarding flow dynamics
and the morphology of the pulmonary circulation, including lung
perfusion status, were reliably assessed (Figure 5).
45
The versatility of this technique was further assessed in the study
of Mohrs et al
46
during which single-breath-hold dynamic imaging was performed in 20
adult patients with a variety of congenital anomalies of the great
vessels, cardiac chambers, and pulmonary-systemic communications.
Despite the diversity of types of pathology encountered, TR-MRA
performed very well in this regard, providing vital anatomic and
qualitative functional information.

TR-MRA of hemodialysis grafts/fistulas

Early attempts at applying MRA to the evaluation of upper
extremity hemodialysis shunts were limited by restrictions in the
FOV attainable prior to the advent of parallel imaging techniques.
This was further compounded by the presence of rapid arteriovenous
transit time, relative to the poor temporal resolution of "static"
high-resolution CE-MRA. The subsequent realization of large-FOV
high-resolution TR-MRA has obviated the need for the previously
attempted technique of multistation shunt assessment. Zhang et al
47
applied 3D TR-MRA using parallel imaging to the assessment of 9
malfunctioning upper extremity AV accesses at 1.5T; this technique
provided single-station entire inflow-outflow morphologic and
functional evaluation, using a single-contrast injection. A high
level of intermodality agreement was found when this technique was
compared with conventional DSA. These sentiments were later echoed
in the studies of Pinto
48
and Mende.
49
At present, concerns regarding the administration of
gadolinium-based contrast media in patients with severe renal
impairment abound in the literature, thus making the role of this
technique in the evaluation of these patients uncertain. However,
the opportunity for reduced contrast doses at higherfield strengths
and the versatility of this technique make it a problem-solving
tool of considerable potential.

Conclusion

The considerable attributes of TR-MRA have been recognized and
embraced over a number of years. It is set to play a central role
in routine clinical vascular assessment. While the versatility of
TR-MRA continues to expand (Figure 6), advances in MR technology
have positioned it as one of the imaging techniques of the future,
allowing single-injection, large-FOV, functional vascular
assessment with minimal contrast doses.